5-(1,1-Difluoroethyl)-3-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,2,4-oxadiazole | 935273-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(1,1-Difluoroethyl)-3-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,2,4-oxadiazole
• 英文别名: 5-(1,1-Difluoroethyl)-3-[4-[4-methyl-5-[2-(trifluoromethyl)phenyl]-1,2,4-triazol-3-yl]-1-bicyclo[2.2.2]octanyl]-1,2,4-oxadiazole
• CAS: 935273-78-2
• 化学式: C₂₂H₂₂F₅N₅O
• 分子量: 467.442
• InChiKey: AHAIJYTWSYJSSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(4-甲基-5-(2-(三氟甲基)苯基)-4H-1,2,4-噻唑-3-基)双环[2.2.2]辛烷-1-羧酸 在 ammonium hydroxide 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 生成 5-(1,1-Difluoroethyl)-3-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension

  摘要：

  In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11 beta-HSD1 inhibitors, we examined a set of 11 beta-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11 beta-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11 beta-HSD1 independent pathway. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.011

文献信息

• HETEROCYCLIC DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Isabel Elise

  公开号：US20110301143A1

  公开（公告）日：2011-12-08

  Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R 1 — substituted heteroaryl, R 1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N—CR 5 R 6 , C═CR 5 or CR 13 —CR 5 R 6 , Y is a bond or —C(O)—, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.

  结构式（I）的杂环化合物，或其药学上可接受的盐，其中W是R1-取代的杂芳基，R1是取代有酯基或羧基的杂芳基环，X-T是N—CR5R6，C═CR5或CR13—CR5R6，Y是键或—C(O)—，a和b代表选自1到4的整数，Ar是可选择取代的苯基或萘基，是硬脂酰辅酶A 9-脱饱和酶（SCD）的抑制剂。这些杂环化合物对于预防和治疗与异常脂质合成和代谢有关的疾病非常有用，包括心血管疾病、动脉粥样硬化、肥胖症、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗、癌症、肝脂肪变性和非酒精性脂肪肝。
• [EN] SUBSTITUTED SEVEN-MEMBERED HETEROCYCLIC COMPOUNDS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OF DIABETES<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES SUBSTITUÉS À SEPT CHAÎNONS EN TANT QU'INHIBITEURS DE LA DIPEPTIDYL-PEPTIDASE IV POUR LE TRAITEMENT DU DIABÈTE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011146358A1

  公开（公告）日：2011-11-24

  The present invention is directed to novel amino-substituted seven-membered heterocyclic compounds of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及结构式（I）的新型氨基取代的七元杂环化合物，这些化合物是二肽基肽酶-IV酶的抑制剂，并且在治疗或预防二肽基肽酶-IV酶参与的疾病中有用，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗二肽基肽酶-IV酶参与的这类疾病中使用这些化合物和组合物。
• AMINOTETRAHYDROPYRANS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  申请人：Biftu Tesfaye

  公开号：US20100120863A1

  公开（公告）日：2010-05-13

  The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及结构式I的新型取代氨基四氢吡喃衍生物，它们是二肽基肽酶-IV酶的抑制剂，可用于治疗或预防二肽基肽酶-IV酶参与的疾病，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗二肽基肽酶-IV酶参与的疾病中的用途。
• [EN] AMINOTETRAHYDROPYRANS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] AMINOTÉTRAHYDROPANES UTILISÉS COMME INHIBITEURS DE LA DIPEPTYL PEPTIDASE-IV POUR TRAITER OU PRÉVENIR LE DIABÈTE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011028455A1

  公开（公告）日：2011-03-10

  The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及结构式I的新型取代氨基四氢吡喃衍生物，它们是二肽基肽酶-IV酶的抑制剂，并且在治疗或预防二肽基肽酶-IV酶参与的疾病，如糖尿病，特别是2型糖尿病方面具有用途。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗二肽基肽酶-IV酶参与的这类疾病中使用这些化合物和组合物。
• [EN] SPIROCYCLIC COMPOUNDS<br/>[FR] COMPOSÉS SPIROCYCLIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2012009217A1

  公开（公告）日：2012-01-19

  Described herein are compounds of formula (I) (Formula (I)). The compounds of formula (I) act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.

  本文描述了式（I）（化学式（I））的化合物。式（I）的化合物作为DGAT1抑制剂，可用于预防、治疗或作为高脂血症、糖尿病和肥胖的疗效剂。